Design

Prospective intervention study

Participants

Twenty-five Caucasian adults with CIPN during or after chemotherapy with potentially neurotoxic agents; patients were enrolled in the study at the first clinical manifestation of neuropathy. The diagnosis of CIPN was based on the National Cancer Institute-Common Toxicity Criteria for Adverse Event (NCI-CTCAE) v4.0 grade of ≥1 for sensory neuropathy, with at least a report of paresthesia of fingers or toes (a criterion for grade 1).

Inclusion criteria were as follows: 18 years or older; Karnofsky performance score >70; treatment with one of the following agents: paclitaxel, docetaxel, nab-paclitaxel, oxaplatin, cisplatin, carboplatin, vinorelbine, vincristine, etoposide, eribulin mesylate; CIPN that evolved after or during standard chemotherapy. Twenty-three patients (92%) received chemotherapy with a neurotoxic agent at enrollment, while 2 patients (8%) had completed chemotherapy with a neurotoxic drug.

Intervention

All patients were required to take an OPERA® capsule once a day, without regard to administration of food.

Study parameters assessed

Chemotherapy-induced peripheral neuropathy was assessed at the enrollment visit and repeated every 3 weeks until 12 weeks, using the following: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) v3.0, sensory and motor neuropathy score; the Total Neuropathy Score clinical version (TNSc); and the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory summary score (mISS). The Visual Analog Scale (VAS) for pain was used to assess pain intensity.

Primary outcome measures

Primary endpoint was the evaluation of changes of measured scores after 12 weeks of therapy compared to baseline evaluation. Secondary endpoints were the evaluation of neuropathy reduction at 12 weeks after beginning of therapy with OPERA®.

Key findings

OPERA® dietary supplement was able to improve CIPN symptoms in a prospective case series of patients treated with neurotoxic chemotherapy, with no significant toxicity or interaction. In addition, no worsening of pain or CIPN symptoms was reported with use of OPERA®. There was no statistical analysis performed for this study.

Practice implications

Chemotherapy-induced peripheral neuropathy describes damage to the peripheral nervous system incurred by a patient who has received a neurotoxic chemotherapeutic agent. It is a frequent dose-limiting side effect for cancer patients treated with platinum-derived compounds, vinca alkaloids, taxanes, and the proteasome inhibitors.1 Neurotoxicity incidence varies depending on the agent used and cumulative dose, with rates ranging from 19% to more than 85% in patients treated with multiple agents.2 A recent meta-analysis showed a CIPN prevalence of 68.1% (95% CI: 57.7-78.4) within the first month post-chemotherapy, 60.0% at 3 months, and 30.0% at 6 months or later.3

No reliably effective treatment has been established to prevent or treat CIPN symptoms. Duloxetine has provided only modest benefit and has associated side effects and a high dropout rate. The 2014 American Society of Clinical Oncology CIPN guideline gives a moderate recommendation for treatment with duloxetin, and recommends further research in this area.4 New safe and effective treatments are needed.

Increased interest in CIPN has included the investigation of several nonpharmaceutical interventions. This study evaluates the dietary supplement OPERA® to treat CIPN. While the authors established the efficacy and safety of OPERA® for CIPN, there are several restrictive variables. There is limited and conflicting evidence for the components of OPERA®. Alpha-lipoic acid has been shown to boost levels of glutathione and support healthy nerve tissue and blood sugar levels.5 Boswellia serrata is a potent anti-inflammatory herb and helps to balance the activity of 5-lipoxygenase (LOX) and support a healthy inflammatory response.6 Methylsulfonylmethane has been shown to reduce C-fiber nerve conduction,7 which is essential for effective pain control. It also has chemopreventive properties and anti-inflammatory activities.8,9

No reliably effective treatment has been established to prevent or treat CIPN symptoms.

The components of OPERA® may work synergistically to improve the symptoms of CIPN because they collectively have anti-inflammatory effects, potent antioxidant properties, and potential benefit for diabetic neuropathy (nerve health and blood sugar control); however, evidence is lacking for the effectiveness of these constituents individually for the use of CIPN. A clear limitation of this study is its small sample size and nonhomogeneous patient population. Despite these limitations, the authors claim that OPERA® reduced patients’ perception of pain, improved motor and sensory impairments, and was well-tolerated, with no treatment-related toxicities. Unfortunately, the authors failed to statistically analyze their results. Lack of statistical significance makes these seemingly positive outcomes impossible to interpret.

While the authors of this study report that OPERA® was safe and effective, these results are not significant given the lack of statistical analysis. The activity of this dietary supplement may benefit patients with CIPN, but future well-designed, prospective, randomized controlled trials are warranted to support its use in these patients.

About the Author

Miranda LaBant, ND, graduated from National University of the Health Sciences in Lombard, Illinois. She is licensed in the state of Hawaii and began her 2-year naturopathic oncology residency program at Lokahi Health Center under the direction of Michael Traub, ND, in Kailua Kona this spring. She was born and raised in Northeast Ohio, where she completed her masters of health sciences from Cleveland State University before pursuing her degree in naturopathy. LaBant is passionate about endocrine and gastrointestinal health, integrative oncology, preventative health and wellness, and the use of botanical medicine and biotherapeutic drainage therapies. In her time outside of the office she can be found exploring and hiking the many landscapes of the Big Island.